Advertisement

Huntington's disease: Mortality and risk factors in an Australian cohort

Published:September 25, 2022DOI:https://doi.org/10.1016/j.jns.2022.120437

      Highlights

      • Median survival from onset was 19 years.
      • There was a 6 times increased risk of death compared to the general population in Australia.
      • CAG repeat number and age of onset were not predictors of association for mortality.

      Abstract

      Introduction

      There has not been any examination of the risk factors associated with mortality in Huntington's Disease (HD) in an Australian cohort.

      Method

      This retrospective study included inpatients admitted to a specialist neuropsychiatry service in Melbourne, Australia. HD status was based on genetic testing. Risk factors included age of onset, CAG repeat length and neuroimaging. Mortality data was acquired through the Australian Institute of Health and Welfare National Death Index.

      Results

      The cohort included 83 participants, with 44 (53%) deceased. The median age of death was 59 years and median survival was 18.8 years from onset age (median 41.0 years). CAG repeat length (median 44.0, IQR 42.5, 47.0) was inversely correlated with age of onset (r = −0.73) and age at death (r = −0.80) but was not correlated with mortality status. There was no difference in functional and cognitive assessments, nor brain volumes, in the alive group compared to the deceased group. There were more people who were alive who had a positive family history of a psychiatric condition (p = 0.006) or dementia (p = 0.009). Standardised mortality ratios demonstrated a 5.9× increased risk of death for those with HD compared to the general population.

      Conclusions

      This is the first study to examine risk factors of mortality in HD in an Australian cohort. Median survival in our cohort is consistent with previous studies in HD, and markedly reduced compared to the general Australian population. CAG repeat length was not associated with mortality suggesting that non-genetic factors contribute to mortality status and warrant further investigation.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Pringsheim T.
        • Wiltshire K.
        • Day L.
        • et al.
        The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis.
        Mov. Disord. 2012; 27: 1083-1091
        • Rawlins M.D.
        • Wexler N.S.
        • Wexler A.R.
        • et al.
        The prevalence of Huntington’s disease.
        Neuroepidemiology. 2016; 46: 144-153
        • Rodrigues F.B.
        • Abreu D.
        • Damásio J.
        • et al.
        Survival, mortality, causes and places of death in a European Huntington’s disease prospective cohort.
        Mov Disord Clin Pract. 2017; 4: 737-742
        • Solberg O.K.
        • Filkuková P.
        • Frich J.C.
        • et al.
        Age at death and causes of death in patients with Huntington disease in Norway in 1986-2015.
        J Huntingtons Dis. 2018; 7: 77-86
        • Paulsen J.S.
        Cognitive impairment in Huntington disease: diagnosis and treatment.
        Curr Neurol Neurosci Rep. 2011; 11: 474-483
        • MacDonald M.E.
        • Ambrose C.M.
        • Duyao M.P.
        • et al.
        A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes.
        Cell. 1993; 72: 971-983
        • Kay C.
        • Collins J.A.
        • Miedzybrodzka Z.
        • et al.
        Huntington disease reduced penetrance alleles occur at high frequency in the general population.
        Neurology. 2016; 87: 282-288
        • Keum J.W.
        • Shin A.
        • Gillis T.
        • et al.
        The HTT CAG-expansion mutation determines age at death but not disease duration in Huntington disease.
        Am. J. Hum. Genet. 2016; 98: 287-298
        • Myers R.H.
        Huntington’s disease genetics.
        NeuroRx. 2004; 1: 255-262
        • Rinaldi C.
        • Salvatore E.
        • Giordano I.
        • et al.
        Predictors of survival in a Huntington’s disease population from southern Italy.
        Can J Neurol Sci. 2012; 39: 48-51
        • Imaizumi Y.
        Mortality rate of Huntington disease in Japan: secular trends, marital status, and geographical variations.
        Jpn. J. Hum. Genet. 1989; 34: 169-178
        • Lanska D.J.
        • Lanska M.J.
        • Lavine L.
        • et al.
        Conditions associated with Huntington’s disease at death. A case-control study.
        Arch Neurol. 1988; 45: 878-880
        • Lanska D.J.
        • Lavine L.
        • Lanska M.J.
        • et al.
        Huntington’s disease mortality in the United States.
        Neurology. 1988; 38: 769-772
        • van den Bogaard S.J.A.
        • Dumas E.M.
        • Acharya T.P.
        • et al.
        Early atrophy of pallidum and accumbens nucleus in Huntington’s disease.
        J. Neurol. 2011; 258: 412-420
        • Rosas H.D.
        • Koroshetz W.J.
        • Chen Y.I.
        • et al.
        Evidence for more widespread cerebral pathology in early HD.
        Neurology. 2003; 60: 1615
        • Müller H.P.
        • Huppertz H.J.
        • Dreyhaupt J.
        • et al.
        Combined cerebral atrophy score in Huntington’s disease based on atlas-based MRI volumetry: sample size calculations for clinical trials.
        Parkinsonism Relat. Disord. 2019; 63: 179-184
        • Gaillard F.
        • Saber M.
        Frontal horn width to intercaudate distance ratio.
        Radiopaedia, 2021 ([Reference article]. Radiopaedia.org, https://doi.org/10.53347/rID-28842)
        • Gaillard F.
        • Haouimi A.
        Intercaudate distance to inner table width ratio.
        Radiopaedia, 2021 ([Reference article]. Radiopaedia.org), https://doi.org/10.53347/rID-28843
        • Loi S.M.
        • Tsoukra P.
        • Chen Z.
        • et al.
        Mortality in dementia is predicted by older age of onset and cognitive presentation.
        Australian & New Zealand Journal of Psychiatry. 2022; 56 (00048674211041003): 852-861https://doi.org/10.1177/00048674211041003
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.
        J. Psychiatr. Res. 1975; 12: 189-198
        • Walterfang M.
        • Siu R.
        • Velakoulis D.
        The NUCOG: validity and reliability of a brief cognitive screening tool in neuropsychiatric patients.
        Aust N Z J Psychiatry. 2006; 40: 995-1002
        • Elgafy H.
        • Bransford R.J.
        • McGuire R.A.
        • et al.
        Blood loss in major spine surgery: are there effective measures to decrease massive hemorrhage in major spine fusion surgery?.
        Spine. 2010; 35: S47-S56
      1. American Psychiatric Association a. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association Washington, DC1980
        • Australian Bureau of Statistics
        Australian Standard of Classification of Cultural and Ethnic Groups.
        (Available from:)
        • Manjón J.V.
        • Coupé P.
        volBrain: an online MRI brain volumetry system.
        Front. in Neuroinforma. 2016; 10
        • Penney Jr., J.B.
        • Vonsattel J.-P.
        • Macdonald M.E.
        • et al.
        CAG repeat number governs the development rate of pathology in Huntington’s disease.
        Ann. Neurol. 1997; 41: 689-692
        • Hosmer D.L.
        • Stanley
        • May Susanne
        Applied Survival Analysis: Regression Modeling of Time-to-Event Data.
        2nd ed. Somerset: Wiley - Interscience, 2008
        • Heemskerk A.-W.
        • Roos R.A.C.
        E04 causes of death in Huntington’s disease.
        Journal of Neurology, Neurosurgery; Psychiatry. 2010; 81: A22
        • Kim H.-J.
        • Shin C.-W.
        • Jeon B.
        • et al.
        Survival of Korean Huntington’s disease patients.
        J Mov Disord. 2016; 9: 166-170
        • Pekmezovic T.
        • Svetel M.
        • Maric J.
        • et al.
        Survival of Huntington’s disease patients in Serbia: longer survival in female patients.
        Eur. J. Epidemiol. 2007; 22: 523-526
        • Chaganti S.S.
        • McCusker E.A.
        • Loy C.T.
        What do we know about late onset Huntington’s disease?.
        J Huntingtons Dis. 2017; 6: 95-103
        • Cruickshank T.
        • Bartlett D.
        • Govus A.
        • et al.
        The relationship between lifestyle and serum neurofilament light protein in Huntington’s disease.
        Brain Behav. 2020; 10e01578
        • Lu A.T.
        • Narayan P.
        • Grant M.J.
        • et al.
        DNA methylation study of Huntington’s disease and motor progression in patients and in animal models.
        Nat. Commun. 2020; 11: 4529
        • Tippett L.J.
        • Waldvogel H.J.
        • Thomas S.J.
        • et al.
        Striosomes and mood dysfunction in Huntington’s disease.
        Brain. 2007; 130: 206-221
        • Waldvogel H.J.
        • Thu D.
        • Hogg V.
        • et al.
        Selective neurodegeneration, neuropathology and symptom profiles in Huntington’s disease.
        Adv. Exp. Med. Biol. 2012; 769: 141-152
        • Myers R.H.
        • Sax D.S.
        • Koroshetz W.J.
        • et al.
        Factors associated with slow progression in Huntington’s disease.
        Arch. Neurol. 1991; 48: 800-804
        • Zielonka D.
        • Stawinska-Witoszynska B.
        Gender differences in non-sex linked disorders: insights from Huntington’s disease.
        Front. Neurol. 2020; 11: 571
        • Yang J.
        • Chen K.
        • Wei Q.
        • et al.
        Clinical and genetic characteristics in patients with Huntington’s disease from China.
        Neurol. Res. 2016; 38: 916-920
        • Tabrizi S.J.
        • Scahill R.I.
        • Owen G.
        • et al.
        Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington’s disease in the TRACK-HD study: analysis of 36-month observational data.
        Lancet Neurol. 2013; 12: 637-649
        • Paulsen J.S.
        • Long J.D.
        • Ross C.A.
        • et al.
        Prediction of manifest Huntington’s disease with clinical and imaging measures: a prospective observational study.
        Lancet Neurol. 2014; 13: 1193-1201